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Phenotype, a Historical Perspective
P Phenotype, a Historical Perspective Robert J Berry, University College London, London, UK r 2001 Elsevier Inc. All rights reserved. This article is reproduced from the previous edition, volume 1, pp 537–547, r 2001, Elsevier Inc.
Glossary Allele (originally allelomorph) A form of variant (sometimes called a mutation) of a gene. Diploid Individual who has two sets of chromosomes, usually received from different parents, in contrast to a haploid organism such as most microorganisms, the gametophyte stage of higher plants and some parthenogenetic forms (e.g., male ants and honeybees). It may have the same form or allele of a gene on both members of a chromosome pair (in which case it is homozygous) in different forms (alleles) (in which case it is heterozygous). Gene Historically, the inherited factor which determines a trait. Tends to be used somewhat loosely; more strictly represents a place or locus on the chromosomes which codes for a particular function.
Background Phenotypes are the appearance and properties of real animals and plantsFliving and dying, reproducing and bearing fruit, and succeeding or failingFbut in themselves they are the products of interactions between the inherited (genetic) material and the environment, both before and after birth. The distinction between genotype and phenotype is one of the more important ones in biology: A phenotype may be produced by several different genotypes, whereas a genotype may manifest as several different phenotypes, particularly when reacting with different environments. The distinction between inherited constitution and external appearance (i.e., between genotype and phenotype) was one of the most important demonstrations of Gregor Mendel (1822–1884) in his series of breeding experiments with peas which laid the foundation for genetics, and in which he recognized that a character may be inherited in a dominant or a recessive manner. An organism manifesting a dominantly inherited trait (in Mendel’s case, round as opposed to wrinkled pods or colored as opposed to white flowers; more familiar examples are brown versus blue eyes in humans or brown coat color versus albino in rabbits or mice) may carry both alleles
Encyclopedia of Biodiversity, Volume 6
Gene (strictly allele) frequency The frequency of an allele in a population. Genome The total genetic composition of an individual. Genotype The allelic composition of an individual at a particular locus. Mutation Change in an allele, producing a different allele; rate of occurrence affected both physically (especially by ionizing radiation) and by many chemicals. It may also refer to changes in a chromosome (involving duplication, deletion, or inversion of a segment). Phenetics The study of phenotypes, usually describing the grouping of organisms into taxa on the basis of estimates of similarity. Phenotype The appearance (function or behavior) of an organism.
for the dominant trait or one for the dominant and one for the recessive trait. That is, it will have the same phenotype but could be genetically homozygous or heterozygous. A distinction between genes and their manifestation was also implicit in August Weismann’s (1834–1914) embryological division between germplasm (which gives rise to reproductive cells) and soma (or body). However, the formal nomenclature phenotype and genotype was devised by the Danish botanist Wilhelm Johannsen (1857–1927), who introduced the word gene for the material basis of an inherited character, and thence the terms genotype and phenotype. Johannsen set out to investigate the relationship between (phenotypic) variation and selection. The rediscovery of Mendel’s work in 1900 led to a rift between the biometricians [notably Karl Pearson (1857–1936) and W. F. R. Weldon (1860–1906)], who followed Darwin (1809–1882) in viewing small continuous variation as the raw material of evolution, and the ‘‘mendelists’’ (or geneticists) [led by William Bateson, (1861–1926)], who believed that large discontinous saltations (or mutations) were the main cause of variation. The problem was the maintenance of continuous variation. Darwin had postulated a continuous replenishment of variation in order for selection to act, but he did not know its source. His
http://dx.doi.org/10.1016/B978-0-12-384719-5.00107-6
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Phenotype, a Historical Perspective
proposal of ‘‘pangenes’’ was an effort to solve the problem. Weismann’s demonstration of the early separation in development of the reproductive tissue from the rest of the body supported the general assumption at the time that continuous variation was produced by environmental effects. Intraspecific variation (i.e., subspecies or local races) was therefore regarded as environmentally caused; the species was viewed as monotypic in a way that had much in common with the preDarwinian ideal or Linnean type. Johannsen experimented with a self-fertilized cultivar of the bean Phaseolus vulgaris. The implication of this was that all the descendants of a single individual would have the same genes and constitute what Johannsen called a ‘‘pure line.’’ Although individual beans might be different (due, for example, to their place in the pod), the mean and variance of all the characters of plants in a pure line were the same and were not affected by attempts at selection, i.e., plants grown from both small beans and large beans produced beans of the same average weight as that of all the plants in the pure line. In contrast, plants grown from crosses between pure lines had different (usually intermediate) characteristics from the parents, although these characteristics remained constant in pure lines derived from each cross. Johannsen argued that selection on continuous variation was inevitably ineffective, and the only variation on which selection could work depended on new mutation. This strengthened the contemporary assumption that evolution was bound up with mutations and their rate of occurrence, and that individuals were largely genetically uniform (i.e., homozygous at most loci for ‘‘wild-type’’ alleles). This assumption became built into conventional population genetic theory so that when recessive traits manifested in inbred populations (usually in the laboratory or garden, but occasionally appearing under wild conditions) they were assumed to be recent mutations in the process of elimination by natural selection. Most mutations seemed to be deleterious to their carriers (which would be expected if they were random changes in a functioning organism), which meant that high mutation rates would inevitably impose a burden on a population. In 1950, at a time of acute concern about the genetic effects of atomic warfare, H. J. Mu¨ller (1890–1967) proposed the concept of ‘‘genetic load’’ and showed that a doubling of the mutation rate in a slow-reproducing species such as humankind could lead to extinction through genetically caused death. The work of Bateson, Johannsen, and other early geneticists (one of the most influential was the Dutchman Hugo de Vries, 1848–1935) led to the isolation of genetics from evolutionary studies, particularly as represented by paleontology. This was resolved by the theoretical work of Sewall Wright (1889–1988), J. B. S. Haldane (1892–1964), and especially R. A. Fisher (1890–1962). Fisher published significant papers in 1918 and 1922 describing the expected biometrical properties of a Mendelian (i.e., breeding) population and the effects of an allele substitution on a quantitative (i.e., continually varying) character. (The papers were published by the Royal Society of Edinburgh; the first one was rejected by the Royal Society of London on the advice of Karl Pearson and the geneticist R. C. Punnett.) He went on to argue that dominance (and recessivity) are traits that have evolved and
this explains why the majority of new mutations are recessive, detrimental, and have a major effect (i.e., on the phenotype); most of the data available at the time were from laboratory breeding of Drosophila melanogaster. Fisher reasoned that there was no intrinsic reason for a mutation occurring for the first time to be either dominant or recessive; the greatest probability is that it will be intermediate, with an effect somewhere between its expression in double dose (i.e., when homozygous) and the unmodified condition. However, 1. Mutations occur repeatedly at virtually every locus. The rare (approximately 1 in 105) mutational events we observe are recurrences of something that has happened thousands of times in the past. 2. When a mutation occurs, it will almost always be present in the heterozygous condition: If an allele has become relatively common in a population so that a fresh mutation to it has a reasonable chance of occurring in an existing heterozygote, then mutation cannot be the only force influencing its frequency. 3. If a newly arisen allele has a beneficial effect on its carrier, combinations of it with other alleles that increase its effect will have a higher fitness than any which decrease it. This will repeatedly occur so that the architecture of the species will become modified to the extent that any new occurrences of that advantageous allele will always produce the maximum effect in its carrier; this will almost always be in the heterozygous condition. In other words, beneficial characters will be selected for dominance and will also spread to replace the previous expression of the trait. Conversely, alleles which are deleterious in the heterozygote are only likely to be transmitted in combinations in which their effect is least, i.e., there will be selection for a small heterozygous effect (in the direction of recessivity). Fisher put forward these ideas from first principles. They were received skeptically because of the difficulty in believing that selection pressures would be strong enough to allow genes which modify dominance to spread. In pre-1950 days primary selection coefficients were thought to be approximately 0.1 to 1.0% and second-order effects were believed to be much less. Haldane suggested that dominance was more likely to be the effect of alleles with a biochemical or developmental margin of safety becoming the normal allele. Since they could exercise undiminished action when heterozygous, mutant alleles would be recessive and deleterious. However, Fisher’s theory has been proven to be correct on many occasions, and although it may not apply for every allele at every locus it has considerable historical significance in bringing together paleontologists and geneticists, and it has relevance in highlighting an important factor influencing genetical architecture. Fisher was the first to demonstrate the experimental modification of dominance by crossing domestic poultry with wild jungle fowl for five generations. This changed the inheritance of certain characters so that a degree of heterozygous manifestation occurred where complete dominance had previously prevailed. Fisher suggested that the dominance of the traits he studied had been attained during domestication as a result of selection for the more striking heterozygotes.
Phenotype, a Historical Perspective
A more complete demonstration of the influences of modifying genes on dominance was performed by E. B. Ford (1901–1985) by breeding from the greatest and least expressions of a variable yellow variant (lutea) of the Currant Moth (Abraxas grossulariata). Although the difference between lutea and non-lutea can be regarded as caused by a single allelic difference, after only three generations of selection Ford produced heterozygotes virtually indistinguishable from the lutea homozygote in selection for the yellowest individuals and ones most like the typical homozygote in the white selection line. In other words, he had changed the heterozygote from a position of no (or intermediate) dominance to complete dominance or recessivity respectively. Ford then crossed his modified heterozygotes with unselected stock, and by the second generation (when the selected modifiers would have a chance of segregating independently) the original variable heterozygotes reappeared: He thus showed that it was the response of the organism rather than the gene that had changed. Laboratory experiments of this nature have been carried out on a variety of organisms and a range of characters. An experiment particularly informative with regard to genetical architecture in the wild was carried out by H. B. D. Kettlewell (1907–1979) using British and Canadian peppered moths (Biston betularia and Amphydasis cognataria, respectively; these are fully interfertile). Although there is a melanic form (swettaria) in the North American species, it is comparatively restricted in its distribution, and only pale (or typical) moths occur over vast tracts of Canada. When a melanic heterozygote and a typical homozygote of British origin are mated, the offspring are clearly dark or light: The melanic character is a straightforward dominant. Even when the typical moths come from Cornwall in extreme southwest England where melanics have never been reported, only a slight loss of complete dominance occurs and that only after several generations of crossing melanics back to Cornish stock (i.e., back-crossing a melanic from several generations of melanic Cornish cross with a ‘‘pure’’ Cornish parent). This modification consists of some white dots on the normally jet-black wings of the heterozygote. Perhaps significantly, this slight heterozygous expression of the gene gives specimens similar to those caught in the early days of the spread of peppered moth melanism in the mid-nineteenth century and which are now prized collectors’ specimens. This white speckling has long since disappeared in wild-caught British specimens, and modern heterozygotes are indistinguishable from melanic homozygotes. Melanism has become fully dominant during the ensuing decades. However, there has been no opportunity for dominance to evolve in Canadian peppered moths. When British melanics are crossed to Canadian stock (from areas where swettaria does not occur) the first-generation progeny segregate as dark or light in the same way as in a cross between British moths. In the first generation, the dominance modifiers in the British parent will be carried on the chromosomes in the same order as in British stock and produce dominance in the same way. In the next generation, the gametes contain chromosomes which have crossed over between the British and Canadian grandparents. Consequently, in the second generation, the ‘‘switch’’ between pale and black forms does not operate as efficiently. Kettlewell crossed heterozygotes from a British Canadian
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mating with Canadian moths and repeated this back-crossing for four consecutive generations, after which the heterozygotes ranged from black to paleFthere was no sign of dominance. He then reversed the procedure and mated his ‘‘broken-down’’ melanics to British typicals. The dominance of the condition was immediately reestablished: The architecture of the British chromosomes shaped a clear segregation between a dark heterozygote and a pale homozygote. Fisher’s theory has proved correct in many similar experiments in both plants and animals, and although it may not be universally operative it provided the genetical basis for the understanding between disciplines that was needed before the neo-Darwinian synthesis could occur. As late as 1932, T. H. Morgan was asserting that ‘‘natural selection does not play the role of a creative principle in evolution,’’ but 10 years later all but a very few biologists were agreed on an evolutionary theory based firmly on Darwin’s ideas knitted with subsequent developments in genetics. This coming together was described by Julian Huxley as the ‘‘modern synthesis’’ in a book with the same name published in 1942. The synthesis can first be seen in three English books: R. A. Fisher’s Genetical Theory of Natural Selection (1930), E. B. Ford’s Mendelism and Evolution (1931), and J. B. S. Haldane’s Causes of Evolution (1932). It was consolidated in three works from America: Theodosius Dobzhanky’s Genetics and the Origin of Species (1937), Ernst Mayr’s Systematics and the Origin of Species (1942), and George Gaylord Simpson’s Tempo and Mode in Evolution (1944). As Mayr noted, it did not occur as a result of one side being proved right and the others wrong but rather from ‘‘an exchange of the most viable components of the previously competing research traditions.’’
The Making of a Phenotype In the simplest microbial systems, there is a one to one relationship between gene action and phenotype: Change in a gene is likely to produce a change in its product, which will manifest directly in the organism as an altered character, perhaps the loss or modification of an enzyme. Such simple relationships exist in all organisms, however complex. There are more than 200 ‘‘inborn errors of metabolism’’ in humans, each resulting from changes in a particular gene, producing a change of phenotype in the whole organism. For example, albinism is due to the inability to synthesize melanin, which is made from tyrosine under the influence of tyrosinase, which is under the control of a gene on chromosome 11 in humans1; ‘‘classical’’ hemophilia results from the absence of a protein (factor VIII) coded by a gene on the X chromosome. However, most traits are affected by many genes. For example, blood clotting in mammals is effected by a cascade of physiological reactions, each under the control of a different gene(s). Efficient clotting requires all the different stages to be operating, and defects in any stage (especially the genes directing the relevant proteins and enzymes) 1 In fact, human albinism can be due to genes on at least two different chromosomes. There are also mutations at another locus on chromosome 11 which cause albinism, but in this case the tyrosinase enzyme is apparently normal. Both genes produce an albino phenotype, but the phenotypes can be distinguished clinically.
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will lead to a ‘‘bleeding’’ phenotype. In blood clotting it is possible to detect where the error lies because we know the normal determinants of clotting in detail. For most traits we do not have information about the steps in their formation. One of the benefits of genome mapping is that the genetical determinants of complex characters will be analyzable in an orderly way. Currently, most phenotypic analysis is biometric rather than genetic. For example, the tails of house mice may be shortened by mutations at approximately 40 loci. We know the action of many of these genes: Some affect the notochord, some cell division rates, and some inductive relations between endoderm and mesectoderm. We also know that the tail length of mice varies between different inbred strains of mice (which are similar in the genetic sense to Johannsen’s pure lines) and that we can increase or decrease tail length by selecting wild-caught animals or the products of crosses between inbred strains. We do not know which genes are variable (or segregating) in any one population or which genes are being affected by selection. However, it is clear from many selection experiments that the genes affecting any complex trait are distributed throughout the genome (i.e., over many chromosomes) and that selection for any one trait may ‘‘unbalance’’ the genome. The concept of genomic balance (often called genomic or genetic architecture) is important. When a normal outbreeding species, such as maize, sugar beet, poultry, or Drosophila, is made to inbreed by manipulating its breeding system, the individuals characteristically decline in vigor and fertility until they stabilize at a stage before complete homozygosis is approached. The amount of this inbreeding depression varies from one line to another within any species. When two inbred lines are intercrossed, the F1 (i.e., the first-generation progeny) show a considerable increase in vigor and fertility, known as hybrid vigor or heterosis. In general, the F1 phenotype is similar to that in the population from which the inbred strains were derived. If F2’s are raised and inbreeding is resumed, inbreeding depression will again occur, although not necessarily to the same extent as in the original lines. Inbreeding depression is often reflected in increased variability not only between individuals but also among repetitive parts such as bilateral characters in animals and floral morphology in plants; fluctuating asymmetry, in which there are differences between the right and left sides of individuals, is commonly used as a rough indicator of inbreeding. F1’s tend to show decreased variability. Michael Lerner argued that this indicates an innate superiority of heterozygotes over homozygotes, perhaps because of a greater biochemical flexibility in the former. It is a phenomenon which has produced considerable research interest, particularly among marine biologists. Lerner argued that if artificial selection is suspended before much of the variation has been lost (as homozygosity increases) natural selection will tend to restore the character (and hence its genetic determinants) to an equilibrium value, with the mean of the character which was artificially selected tending to revert toward its original value; he called this genetic homeostasis. Artificial selection tends to accumulate alleles which act on a character in a particular way, e.g., to increase its size of or the number of elements making up a repeated trait. If we make the reasonable assumption that any population needs to combine phenotypic uniformity in a stable environment with
long-term flexibility should the environment change, the easiest way to do this is for the character in question to be controlled by alleles at different loci, with some alleles acting to increase the expression of the character and others acting to decrease it. In such a case, Fisher showed that selection will favor linkage between the loci responsible, with the evolution of ‘‘balanced’’ chromosomes containing ‘‘positive’’ and ‘‘negative’’ alleles. The simplest situation will involve two segregating loci, A,a and B,b with A,B acting in one direction and a,b in the other (i.e., additive genes). The intermediate type can be either the attraction or the repulsion heterozygote, AB/ab or Ab/aB. However, the latter will be favored since it will be less likely to produce zygotes giving the extreme phenotypes (Figure 1). For the same reason, any mechanisms bringing about closer linkage between the loci concerned (such as a chromosomal inversion) will be favored. This theoretical arrangement has been subjected to experimental analysis, mainly through selection experiments in Drosophila, and has been generally confirmed; it receives support from the distribution of ‘‘quantitative trait loci’’ identified by molecular techniques. It also accounts for other properties: 1. Selection (natural or artificial) for any character almost invariably produces correlated responses in additional developmentally independent traits of the phenotype. 2. Gene loci affecting viability traits are interspersed along the chromosomes with loci affecting other characters. 3. The highest rate of artificially induced new variation by mutation is many times less than that occurring spontaneously through recombination. 4. There is widespread occurrence of chromosomal inversions in nature. 5. Deleterious gene combinations (even to the point of lethality) may occur solely as a result of recombination. There are a few cases in which the different genes contributing to complex variation have been identified. This has been done for the determinants of the pin thrum polymorphism in Primula vulgaris, in which different members of a linked group of loci control anther height, style length, pollen size, rate of pollen tube growth, and length of the papillae on the stigma; for mimetic patterns in the African swallowtail butterfly Papilio dardanus; and for color and banding patterns in the land snail Cepaea nemoralis. In house mice, approximately 16% of genes with an identified function are concerned with behavior and have been located on 19 of the 20 chromosomes of the species. However, in most cases it is only possible to conclude that different components of a character complex are inherited as a unit, i.e., that the gene complex is coadapted. Coadaptation is presumably the reason why the genomes of interfertile species do not always merge when they meet. For example, races of dark- and light-bellied house mice (referred to as Mus musculus domesticus and M. m. musculus, respectively, although they should perhaps be given full species status) meet in a narrow zone of intergradation across Jutland (Denmark) and south through Germany. Although the two forms readily interbreed in the laboratory, the hybrid zone has apparently been constant for at least 50 years. Gene frequencies on the two sides of the hybrid zone are very different. Remarkably, the frequencies in the light-bellied form in California, which are descended from the same stock as the light-bellied Danish
Phenotype, a Historical Perspective
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Figure 1 Effect of linkage on the incidence of the extremes of manifestation of an additively inherited character. If A,B produce a phenotype effect of 1 and a,b an effect of 0, the matings between two repulsion heterozygotes are least likely to produce extreme phenotypes (they will only appear if recombination between the two loci occurs in both parents).
animals, are more like those in the light-bellied Danish population than are the light-bellied Danish ones from their dark-bellied neighbors. A similar situation exists in deer mice (Peromyscus polionotus) in Florida and also in carrion and hooded crows in the same area in which the dark- and light-bellied mice occur in Europe. However, some species lose their identity wholly when brought into breeding contact. This has happened commonly in New Zealand, where much of the terrestrial biota has been introduced. Hybrid zones are common. Presumably these occur when coadaptation has not evolved.
Formal Analysis In the past, it was suggested that the genes which control major or qualitative traits are different from those which affect quantitative ones (oligogenes and polygenes, respectively). This distinction is now rarely made. In other words, it is assumed that genes affecting quantitative traits (such as weight or size or physiological properties such as metabolic rate) follow Mendelian patterns of inheritance, may have multiple alleles, can mutate, change in gene frequency, show dominance, etc. Quantitative inheritance is merely a general case of the interaction of genes in which the interacting components are little or wholly known. The number of genes which affect a trait can be estimated by the amount and speed of response in a selection experiment or by the mean and variance of the character as measured in a population. Using these techniques it has been calculated that human skin color may be determined by only 5 or 6 loci,
whereas the number of genes affecting oil and protein production in maize may be as high as 54 and 122, respectively. However, such estimates are very dependent on the nature of interactions between the loci concerned and should be regarded as no more than suggestive of a large or small number. The simplest assumption in multigenic trait determination is that all the loci affect the trait equally and therefore additively. However, detailed analysis has shown that in many (perhaps most) cases, a few genes have a major effect and many genes have a minor effect. For example, in the well-studied case of variation in sternopleural bristle number in D. melanogaster, approximately 10 loci account for 75% of the genetic variation in number. The situation is further complicated by pleiotropy: A gene may have a major effect on one character but minor effects on others. For example, phenylketonuria is an inborn error of metabolism producing severe mental retardation in humans and is produced by the nonfunctioning of phenylalanine hydroxylase, which is controlled as a recessive trait by a single gene on chromosome 12. The same enzyme is involved in melanin synthesis, and phenylketonurics have slightly paler hair and complexion than their normal sibs. The gene can therefore be regarded as having a major effect on intelligence but a minor effect on pigmentation. However, a quantitatively inherited trait will be more likely than a qualitative one to be affected by environment. A group of individuals having identical genes for growth (i.e., a pure line or a clone) may show considerable variation in size due to differences in available nutrients. Although the same potential for size is present in the initial gene products, the manifestation of the phenotype will be limited by such factors as food availability.
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Phenotype, a Historical Perspective
Conversely, a population of genetically heterogeneous individuals may grow to the same size if no gene–environment interaction is limiting (or if different interactions compensate for each other). Generalizing, we can express the phenotypic value P for individual i in environment j as Pij ¼ Gi þ Ej where Gi is the genetic contribution of the jth genotype and Ej is the environmental deviation resulting from the jth environment. A particular genotype may do well in a particular environment, implying a specific interaction between the two. In this case, Pij ¼ Gi þ Ej þ GEij In practice, there will be variance of these components so that Vp ¼ VG þ VE þ 2CovGE where Vp, VG, VE, and 2CovGE, are the phenotypic, genetic, and environmental variance and the genotype–environment covariance, respectively. The genotype–environment covariance is positive when genotypes with higher values are in better environments and poorer genotypes have poorer environments. This may occur in animals when one member of a litter is large because of its genes and gets more food from its parents or when an animal is socially dominant for genetic reasons and therefore has more resources in food and spaces. A plant genotype which grows faster may have a better environment because it is less likely to be shaded. In controlled plant and animal breeding, efforts are made to randomize genotypes and environments, so that CovGE is minimized. In this situation, CovGE can be neglected, and Vp ¼ VG þ VE Conventionally, VG =VP þ VE =VP ¼ h2 þ e2 where h2 and e2 are the proportion of phenotypic variation due to genetic and environmental factors, respectively. The term h2 is known as heritability in the broad sense, h2B ¼ VG =VP In practice the genetic variance is composed of a range of different interactions between loci, which may be additive, dominant, or epistatic. Variability in the narrow sense is defined as h2N ¼ VA =VP where VA is the variance due to additive genetic factors. It is an important statistic in determining the rate and amount of response to directional selection in breeding programs. Heritability is a population-specific measurement. It does not measure an invariant property of a particular trait but only the relative contributions of genetic and environmental differences to phenotypic variation in a specific situation. If either genetic or environmental variation changes, heritability estimates will also change; heritability measures the proportion of phenotypic variation in a particular population due to genetic variation.
Genetic and Phenotypic Variability The assumption of the early geneticists that most populations carry little variation and that most individuals are homozygous at all but a few loci at which alleles are either recent mutants in the process of being eliminated by selection or maintained by opposing selection pressures or heterosis is clearly wrong. Evolutionary theory (requiring modifying genes to change phenotype expression) and artificial selection practice (revealing considerable potential for inherited response to selection) imply the existence of considerable genetic variation in and between populations. In the 1950s and 1960s assumptions about genetic load suggested there was a maximum amount of variation which could be tolerated in any population, but the application of protein and later DNA electrophoresis showed that load theory was too narrow and deterministic and led to reinterpretation so as to incorporate ecological factors (including heterogeneity in time and space and variable stress from biotic and abiotic agents). Empirical data have shown that even inbred organisms (such as obligate self-fertilizers) or ones living in an apparently constant environment (such as the deep sea) may still be heterozygous at a significant proportion of their loci (up to one-fourth for enzyme loci in plants and invertebrates and less for vertebrates). The implications of load theory led to debate among population geneticists and evolutionists about the significance of the observed variation. Theoreticians impressed by the apparent rigor of load theory and biochemists not used to meaningful variation in their study of chemical pathways tended to dismiss the bulk of genetic variation as neutral and irrelevant to the organism, whereas evolutionary ecologists and practical breeders regarded it as potentially adaptive and as expected by Darwinian understanding. The latter emphasis has been shown to be correct: Far from being constrained by invariant genotypes, phenotypes can (and should) be treated as capable of rapid response to the environment and hence permissive rather than determinative of survival. A phenotype can be interpreted as the consequence of developmental reaction norms, facilitated in most cases by the width of its underlying genetic base. This concept is supported by a series of experiments carried out by Bruce Wallace to test if radiation-induced mutations in D. melanogaster were inevitably detrimental. He found that mutations induced in flies made homozygous by artificial breeding were often heterotic, although mutations occurring in flies with a heterozygous background were usually deleterious to their carriers, presumably since their gene expression had been adjusted by normal selection. This led Wallace to emphasize the importance of balancing (or stabilizing) selection rather than the directed or cleansing selection which removes unwanted variants. The concept of reaction norm incorporates the idea of phenotypic plasticity championed by Bradshaw and Levins in the 1960s and provides a much needed synthesis of allometry and ontogeny with ecological realism and fitness components. A particularly good example is the seasonal polyphenism of the African satyrine butterfly, Bicyclus anyana, studied by Paul Brakefield and colleagues. The wet and dry season forms of this species are phenotypically distinct in the size of the
Phenotype, a Historical Perspective
eyespots and the banding patterns on the wings. Seasonal shifts in rainfall are associated with changes in temperature and with butterfly behavior. In the cooler dry season, the insects rest on dry grass or leaf litter and rarely fly; they do not breed at this time. In contrast, the adults fly actively in the warmer wet season, searching for mates and oviposition sites in the lush vegetation. Survival differences between the two forms suggest that cryptic matching is more important in the dry season and deception mediated by the false eyes in the wet season. The wet season form arises through an acceleration of development which can result from an increased or fluctuating temperature, food quality, or hormonal influence. However, eyespot size and plasticity are affected by genetic variation as shown by variation between families in different temperature regimes and by directed selection. The switch between different wing spotting phenotypes in the butterfly Maniola jurtina studied over many years by E. B. Ford is probably also of this nature. Ford’s extensive field studies showed the interaction between founder population differentiation, natural selection in particular localities, and environmental determinants, although he did not interpret them in this way. Unlike the Bicyclus case, the changes in phenotype in Maniola are small and unlikely to be important in survival or fitness (although it would be wrong to be dogmatic about this conclusion). However, they serve as a marker of a variable developmental system which may well have a range of functional responses. There are many such examples of trivial (or even wholly cryptic) differences between individuals which have different functional properties (e.g., the possession of B chromosomes or resistance to a newly introduced pesticide or pathogen). The complicated response system in Bicyclus (and other butterflies) is similar in principle to the much simpler situation of eye pigmentation in the amphipod Gammarus chevreuxi studied classically by Julian Huxley and Ford. Here, the unpigmented, red-eye form is produced by a single mutant allele which has a slower rate of melanin synthesis than normal. However, pigmented eyes like the wild type arise if genetically red-eyed animals are raised at higher temperatures than normal or if they also carry a gene for small eyes which enables the small amount of pigment produced to cover the whole eye. Another example is the ‘‘himalayan’’ mutation of mammals frequently described in elementary genetics textbooks in which an unpigmented (white) coat becomes pigmented at the cold extremities (feet and ears), as in Siamese cats. Pigmentation may also develop in hair which grows in a shaved area which has a lower temperature than usual. The tyrosinase in this genotype is heat labile and has a maximum activity below normal body temperature. Rate genes of this nature have been very important in evolution and can be shown to produce major alterations in body form through various forms of allometry.
Phenotypes and Evolution It is a truism that natural selection can only operate where phenotypic variation exists. Evolution results from changes in gene (strictly allele) frequencies, but these are the consequence rather than the cause of phenotypic differences. It follows that
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selection on local forms (or ecotypes) which are solely the environmental consequence of a particular environment (e.g., plants grown in sheltered or exposed conditions or subject to a particular dietary lack or a behavioral reaction in an animal) will not lead to adaptive adjustment unless the phenotype in question depends on different genotypes. However, a phenotypic response to environmental conditions may allow a genetically nonadapted population to survive long enough to accumulate variants (through mutation, recombination, or immigration) and then adapt genetically. This idea was put forward independently by Baldwin (1896), Osborn (1897), and Lloyd Morgan (1900): It is commonly known as the Principle of Organic Selection or the Baldwin effect. This has been claimed by some to bridge the directed response which is the basis of Lamarckism and the random source of inherited variation which underlies Darwinism. Certainly, it may mimic Lamarckism, although it is of course wholly Darwinian in its operation. Most of the early studies of phenotypic plasticity were carried out by botanists: Gaston Bonnier in the Alps and Pyrenees, F. E. Clements in Colorado and California, Turesson in Sweden, and Clausen, Keck, and Hiesey in California. However, the evolutionary implications were not pursued until Gause and Schmalhaussen in Russia and Waddington in Britain began to examine the relationships between genotype, phenotype, and environment in animal experiments. They were able to show not only that natural selection could lead to a character originally induced by the environment becoming an inherited character (Waddington called this ‘‘genetic assimilation’’) but also that there is a causal connection between the environmentally induced change and subsequent genetic changes. They argued that since adaptabilityFthe ability to acquire an adaptive variant during an animal’s lifetimeFhas a genetic basis, the genes underlying flexible adaptive variations may ultimately be responsible for the evolution of fixed adaptations to a new environment, i.e., the environment is much more than a sieve selecting (or eliminating) chance mutations. These ideas have been criticized (notably by G. C. Williams) on two grounds: That most changes resulting from environmental challenges are not adaptive and that fixation of a genetic response results in a decrease in genetic potential because less (genetic) information is needed to specify a fixed, than a variable response. There is truth in both these objections, although the assumption that plasticity requires more inherited variation than a fixed state is debatable. However, there is no doubt that the link between stress-generated responses and subsequent adaptation requires more study. The problem historically is that ecologists have been primarily concerned with pattern (i.e., spatial relationships within communities), whereas evolutionists have concentrated on processes (i.e., temporal changes within communities), and both have used restrictive definitions of stress. This division between disciplines is not, of course, absolute, but it has led to a rift within population biology and a lack of understanding of coevolutionary possibilities and constraints. The divergence between ecologists and evolutionists is seen in the models developed by each. In general, ecological models are self-contained because the dependent variables (numbers or density) and parameters (birth and death rates, dispersion differences, rates of predation, etc.) are all
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measurable by ecological methods. Ecologists have been particularly concerned with identifying criteria for stability or fluctuation when species interact, for invadability, and for extinction when competition occurs. Such models are limited because the parameters are all manifestations of the phenotypic properties of individuals and hence the product of evolutionary processes. Although lip service is paid to the fact that phenotypes may change, in practice they are assumed to be effectively constant in ecological time. Evolutionary models originally concentrated on examining possible rates of evolution; then they became concerned more with the factors involved in the maintenance of genetic polymorphism. Their variables are the frequencies of alleles and genotypes; their parameters are relative fitnesses and rates of mutation, migration, and recombination. For a long time, fitnesses were regarded by the model builders as virtually constant, and it is only comparatively recently that the dependence of selection coefficients on density and frequency has been incorporated. This false assumption of constancy led to the problems associated with genetic load and to controversies over neutralism. Genetical (evolutionary) models have become increasingly realistic and treat relative fitnesses as capable of varying in time and space as well as with gene frequency and population density. Such models are both genetical and ecological, and therefore they are intrinsically more informative than purely ecological ones. However, they still suffer from a major problem in that they tend to assume a degree of genetical equilibrium or stasis which is unjustified. The way forward will be to increase ecological reality of evolutionary models, taking into account the characteristics of the niche for particular populations and communities, particularly any genetic constraints. Such models obviously need to include behavioral (sociobiological) input and the notion of evolutionary ‘‘strategies.’’
Taxonomy Classification has become increasingly sophisticated with the increase in traits which can be used to characterize a group (or taxon). The problem is that conventional taxonomic (phenotypic) diversity may bear little relationship to genetic diversity. For example, the seaside sparrow (Ammodramus nigrescens) is common on the eastern and southern coasts of the United States. Nine subspecies have been described, including a rare and recently extinct (1987) dusky form, originally regarded as a separate species. Molecular analysis (based on mitochondrial DNA sequences) showed that the dusky sparrow was indistinguishable from other Atlantic forms, but that there was a major and previously unsuspected distinction between Atlantic and Gulf Coast groups.
In contrast, New Zealand tuatara lizards (Sphenodon punctatus) are conventionally treated as a single taxon, but molecular (and morphological) criteria indicate they comprise at least three species. For conservation management, it is obviously important that each taxon be considered separately. There is no clear correlation between genetic and taxonomic diversity. The problems of classification that have always challenged museum workers have been compounded by the possibility of using genetic factors as additional or substitute taxonomic criteria: Closely related species in the genetic sense may have very different niches than those of their near relatives, whereas genetically more distant forms may look alike and interact strongly. There are no clear rules to link phenotype with genotype or phenotypic variety with genetic variety. There is plenty of scope for better multidisciplinary understanding of phenotypes, this will have to involve genetics, development, behavior, biotic and abiotic environments, life history, and phylogeny. Notwithstanding case by case examinations of the determinants and plasticity of the phenotypes in particular species and species groups are still needed.
See also: Evolution, Theory of. Genes, Description of. Genetic Diversity
References Avise JC (1994) Molecular Markers, Natural History and Evolution. New York: Chapman & Hall. Berry RJ, Crawford TJ, and Hewitt GM (eds.) (1992) Genes in Ecology. Oxford: Blackwell. Briggs D and Walters SM (1984) Plant Variation and Evolution, 2nd ed. Cambridge, UK: Cambridge Univ. Press. Falconer DS (1989) Introduction to Quantitative Genetics, 3rd ed. New York: Longman. Feder ME, Bennett AF, Burggren WW, and Huey RB (eds.) (1987) New Directions in Ecological Physiology. Cambridge, UK: Cambridge Univ. Press. Gould SJ (1977) Ontogeny and Phylogeny. Cambridge, MA: Harvard Univ. Press. Hamilton WD (1996) Narrow Roads of Gene Land. New York: Freeman. Hoffman AA and Parsons PA (1997) Extreme Environmental Change and Evolution. Cambridge, UK: Cambridge Univ. Press. Jablonka E and Lamb MJ (1995) Epigenetic Inheritance and Evolution. Oxford: Oxford Univ. Press. Mather K (1973) Genetical Structure of Populations. London: Chapman & Hall. Mayr E (1982) The Growth of Biological Thought. Cambridge, MA: Harvard Univ. Press. Raff RA (1996) The Shape of Life. Chicago: Univ. of Chicago Press. Schlichting CD and Pigliucci M (1998) Phenotypic Evolution. Sunderland, MA: Sinauer. Waddington CH (1957) The Strategy of the Genes. London: Allen & Unwin. Yablokov AV (1986) Phenetics. New York: Columbia Univ. Press.
Glossary Allele (originally allelomorph) A form of variant (sometimes called a mutation) of a gene. Diploid Individual who has two sets of chromosomes, usually received from different parents, in contrast to a haploid organism such as most microorganisms, the gametophyte stage of higher plants and some parthenogenetic forms (e.g., male ants and honeybees). It may have the same form or allele of a gene on both members of a chromosome pair (in which case it is homozygous) in different forms (alleles) (in which case it is heterozygous). Gene Historically, the inherited factor which determines a trait. Tends to be used somewhat loosely; more strictly represents a place or locus on the chromosomes which codes for a particular function.
Background Phenotypes are the appearance and properties of real animals and plantsFliving and dying, reproducing and bearing fruit, and succeeding or failingFbut in themselves they are the products of interactions between the inherited (genetic) material and the environment, both before and after birth. The distinction between genotype and phenotype is one of the more important ones in biology: A phenotype may be produced by several different genotypes, whereas a genotype may manifest as several different phenotypes, particularly when reacting with different environments. The distinction between inherited constitution and external appearance (i.e., between genotype and phenotype) was one of the most important demonstrations of Gregor Mendel (1822–1884) in his series of breeding experiments with peas which laid the foundation for genetics, and in which he recognized that a character may be inherited in a dominant or a recessive manner. An organism manifesting a dominantly inherited trait (in Mendel’s case, round as opposed to wrinkled pods or colored as opposed to white flowers; more familiar examples are brown versus blue eyes in humans or brown coat color versus albino in rabbits or mice) may carry both alleles
Encyclopedia of Biodiversity, Volume 6
Gene (strictly allele) frequency The frequency of an allele in a population. Genome The total genetic composition of an individual. Genotype The allelic composition of an individual at a particular locus. Mutation Change in an allele, producing a different allele; rate of occurrence affected both physically (especially by ionizing radiation) and by many chemicals. It may also refer to changes in a chromosome (involving duplication, deletion, or inversion of a segment). Phenetics The study of phenotypes, usually describing the grouping of organisms into taxa on the basis of estimates of similarity. Phenotype The appearance (function or behavior) of an organism.
for the dominant trait or one for the dominant and one for the recessive trait. That is, it will have the same phenotype but could be genetically homozygous or heterozygous. A distinction between genes and their manifestation was also implicit in August Weismann’s (1834–1914) embryological division between germplasm (which gives rise to reproductive cells) and soma (or body). However, the formal nomenclature phenotype and genotype was devised by the Danish botanist Wilhelm Johannsen (1857–1927), who introduced the word gene for the material basis of an inherited character, and thence the terms genotype and phenotype. Johannsen set out to investigate the relationship between (phenotypic) variation and selection. The rediscovery of Mendel’s work in 1900 led to a rift between the biometricians [notably Karl Pearson (1857–1936) and W. F. R. Weldon (1860–1906)], who followed Darwin (1809–1882) in viewing small continuous variation as the raw material of evolution, and the ‘‘mendelists’’ (or geneticists) [led by William Bateson, (1861–1926)], who believed that large discontinous saltations (or mutations) were the main cause of variation. The problem was the maintenance of continuous variation. Darwin had postulated a continuous replenishment of variation in order for selection to act, but he did not know its source. His
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proposal of ‘‘pangenes’’ was an effort to solve the problem. Weismann’s demonstration of the early separation in development of the reproductive tissue from the rest of the body supported the general assumption at the time that continuous variation was produced by environmental effects. Intraspecific variation (i.e., subspecies or local races) was therefore regarded as environmentally caused; the species was viewed as monotypic in a way that had much in common with the preDarwinian ideal or Linnean type. Johannsen experimented with a self-fertilized cultivar of the bean Phaseolus vulgaris. The implication of this was that all the descendants of a single individual would have the same genes and constitute what Johannsen called a ‘‘pure line.’’ Although individual beans might be different (due, for example, to their place in the pod), the mean and variance of all the characters of plants in a pure line were the same and were not affected by attempts at selection, i.e., plants grown from both small beans and large beans produced beans of the same average weight as that of all the plants in the pure line. In contrast, plants grown from crosses between pure lines had different (usually intermediate) characteristics from the parents, although these characteristics remained constant in pure lines derived from each cross. Johannsen argued that selection on continuous variation was inevitably ineffective, and the only variation on which selection could work depended on new mutation. This strengthened the contemporary assumption that evolution was bound up with mutations and their rate of occurrence, and that individuals were largely genetically uniform (i.e., homozygous at most loci for ‘‘wild-type’’ alleles). This assumption became built into conventional population genetic theory so that when recessive traits manifested in inbred populations (usually in the laboratory or garden, but occasionally appearing under wild conditions) they were assumed to be recent mutations in the process of elimination by natural selection. Most mutations seemed to be deleterious to their carriers (which would be expected if they were random changes in a functioning organism), which meant that high mutation rates would inevitably impose a burden on a population. In 1950, at a time of acute concern about the genetic effects of atomic warfare, H. J. Mu¨ller (1890–1967) proposed the concept of ‘‘genetic load’’ and showed that a doubling of the mutation rate in a slow-reproducing species such as humankind could lead to extinction through genetically caused death. The work of Bateson, Johannsen, and other early geneticists (one of the most influential was the Dutchman Hugo de Vries, 1848–1935) led to the isolation of genetics from evolutionary studies, particularly as represented by paleontology. This was resolved by the theoretical work of Sewall Wright (1889–1988), J. B. S. Haldane (1892–1964), and especially R. A. Fisher (1890–1962). Fisher published significant papers in 1918 and 1922 describing the expected biometrical properties of a Mendelian (i.e., breeding) population and the effects of an allele substitution on a quantitative (i.e., continually varying) character. (The papers were published by the Royal Society of Edinburgh; the first one was rejected by the Royal Society of London on the advice of Karl Pearson and the geneticist R. C. Punnett.) He went on to argue that dominance (and recessivity) are traits that have evolved and
this explains why the majority of new mutations are recessive, detrimental, and have a major effect (i.e., on the phenotype); most of the data available at the time were from laboratory breeding of Drosophila melanogaster. Fisher reasoned that there was no intrinsic reason for a mutation occurring for the first time to be either dominant or recessive; the greatest probability is that it will be intermediate, with an effect somewhere between its expression in double dose (i.e., when homozygous) and the unmodified condition. However, 1. Mutations occur repeatedly at virtually every locus. The rare (approximately 1 in 105) mutational events we observe are recurrences of something that has happened thousands of times in the past. 2. When a mutation occurs, it will almost always be present in the heterozygous condition: If an allele has become relatively common in a population so that a fresh mutation to it has a reasonable chance of occurring in an existing heterozygote, then mutation cannot be the only force influencing its frequency. 3. If a newly arisen allele has a beneficial effect on its carrier, combinations of it with other alleles that increase its effect will have a higher fitness than any which decrease it. This will repeatedly occur so that the architecture of the species will become modified to the extent that any new occurrences of that advantageous allele will always produce the maximum effect in its carrier; this will almost always be in the heterozygous condition. In other words, beneficial characters will be selected for dominance and will also spread to replace the previous expression of the trait. Conversely, alleles which are deleterious in the heterozygote are only likely to be transmitted in combinations in which their effect is least, i.e., there will be selection for a small heterozygous effect (in the direction of recessivity). Fisher put forward these ideas from first principles. They were received skeptically because of the difficulty in believing that selection pressures would be strong enough to allow genes which modify dominance to spread. In pre-1950 days primary selection coefficients were thought to be approximately 0.1 to 1.0% and second-order effects were believed to be much less. Haldane suggested that dominance was more likely to be the effect of alleles with a biochemical or developmental margin of safety becoming the normal allele. Since they could exercise undiminished action when heterozygous, mutant alleles would be recessive and deleterious. However, Fisher’s theory has been proven to be correct on many occasions, and although it may not apply for every allele at every locus it has considerable historical significance in bringing together paleontologists and geneticists, and it has relevance in highlighting an important factor influencing genetical architecture. Fisher was the first to demonstrate the experimental modification of dominance by crossing domestic poultry with wild jungle fowl for five generations. This changed the inheritance of certain characters so that a degree of heterozygous manifestation occurred where complete dominance had previously prevailed. Fisher suggested that the dominance of the traits he studied had been attained during domestication as a result of selection for the more striking heterozygotes.
Phenotype, a Historical Perspective
A more complete demonstration of the influences of modifying genes on dominance was performed by E. B. Ford (1901–1985) by breeding from the greatest and least expressions of a variable yellow variant (lutea) of the Currant Moth (Abraxas grossulariata). Although the difference between lutea and non-lutea can be regarded as caused by a single allelic difference, after only three generations of selection Ford produced heterozygotes virtually indistinguishable from the lutea homozygote in selection for the yellowest individuals and ones most like the typical homozygote in the white selection line. In other words, he had changed the heterozygote from a position of no (or intermediate) dominance to complete dominance or recessivity respectively. Ford then crossed his modified heterozygotes with unselected stock, and by the second generation (when the selected modifiers would have a chance of segregating independently) the original variable heterozygotes reappeared: He thus showed that it was the response of the organism rather than the gene that had changed. Laboratory experiments of this nature have been carried out on a variety of organisms and a range of characters. An experiment particularly informative with regard to genetical architecture in the wild was carried out by H. B. D. Kettlewell (1907–1979) using British and Canadian peppered moths (Biston betularia and Amphydasis cognataria, respectively; these are fully interfertile). Although there is a melanic form (swettaria) in the North American species, it is comparatively restricted in its distribution, and only pale (or typical) moths occur over vast tracts of Canada. When a melanic heterozygote and a typical homozygote of British origin are mated, the offspring are clearly dark or light: The melanic character is a straightforward dominant. Even when the typical moths come from Cornwall in extreme southwest England where melanics have never been reported, only a slight loss of complete dominance occurs and that only after several generations of crossing melanics back to Cornish stock (i.e., back-crossing a melanic from several generations of melanic Cornish cross with a ‘‘pure’’ Cornish parent). This modification consists of some white dots on the normally jet-black wings of the heterozygote. Perhaps significantly, this slight heterozygous expression of the gene gives specimens similar to those caught in the early days of the spread of peppered moth melanism in the mid-nineteenth century and which are now prized collectors’ specimens. This white speckling has long since disappeared in wild-caught British specimens, and modern heterozygotes are indistinguishable from melanic homozygotes. Melanism has become fully dominant during the ensuing decades. However, there has been no opportunity for dominance to evolve in Canadian peppered moths. When British melanics are crossed to Canadian stock (from areas where swettaria does not occur) the first-generation progeny segregate as dark or light in the same way as in a cross between British moths. In the first generation, the dominance modifiers in the British parent will be carried on the chromosomes in the same order as in British stock and produce dominance in the same way. In the next generation, the gametes contain chromosomes which have crossed over between the British and Canadian grandparents. Consequently, in the second generation, the ‘‘switch’’ between pale and black forms does not operate as efficiently. Kettlewell crossed heterozygotes from a British Canadian
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mating with Canadian moths and repeated this back-crossing for four consecutive generations, after which the heterozygotes ranged from black to paleFthere was no sign of dominance. He then reversed the procedure and mated his ‘‘broken-down’’ melanics to British typicals. The dominance of the condition was immediately reestablished: The architecture of the British chromosomes shaped a clear segregation between a dark heterozygote and a pale homozygote. Fisher’s theory has proved correct in many similar experiments in both plants and animals, and although it may not be universally operative it provided the genetical basis for the understanding between disciplines that was needed before the neo-Darwinian synthesis could occur. As late as 1932, T. H. Morgan was asserting that ‘‘natural selection does not play the role of a creative principle in evolution,’’ but 10 years later all but a very few biologists were agreed on an evolutionary theory based firmly on Darwin’s ideas knitted with subsequent developments in genetics. This coming together was described by Julian Huxley as the ‘‘modern synthesis’’ in a book with the same name published in 1942. The synthesis can first be seen in three English books: R. A. Fisher’s Genetical Theory of Natural Selection (1930), E. B. Ford’s Mendelism and Evolution (1931), and J. B. S. Haldane’s Causes of Evolution (1932). It was consolidated in three works from America: Theodosius Dobzhanky’s Genetics and the Origin of Species (1937), Ernst Mayr’s Systematics and the Origin of Species (1942), and George Gaylord Simpson’s Tempo and Mode in Evolution (1944). As Mayr noted, it did not occur as a result of one side being proved right and the others wrong but rather from ‘‘an exchange of the most viable components of the previously competing research traditions.’’
The Making of a Phenotype In the simplest microbial systems, there is a one to one relationship between gene action and phenotype: Change in a gene is likely to produce a change in its product, which will manifest directly in the organism as an altered character, perhaps the loss or modification of an enzyme. Such simple relationships exist in all organisms, however complex. There are more than 200 ‘‘inborn errors of metabolism’’ in humans, each resulting from changes in a particular gene, producing a change of phenotype in the whole organism. For example, albinism is due to the inability to synthesize melanin, which is made from tyrosine under the influence of tyrosinase, which is under the control of a gene on chromosome 11 in humans1; ‘‘classical’’ hemophilia results from the absence of a protein (factor VIII) coded by a gene on the X chromosome. However, most traits are affected by many genes. For example, blood clotting in mammals is effected by a cascade of physiological reactions, each under the control of a different gene(s). Efficient clotting requires all the different stages to be operating, and defects in any stage (especially the genes directing the relevant proteins and enzymes) 1 In fact, human albinism can be due to genes on at least two different chromosomes. There are also mutations at another locus on chromosome 11 which cause albinism, but in this case the tyrosinase enzyme is apparently normal. Both genes produce an albino phenotype, but the phenotypes can be distinguished clinically.
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will lead to a ‘‘bleeding’’ phenotype. In blood clotting it is possible to detect where the error lies because we know the normal determinants of clotting in detail. For most traits we do not have information about the steps in their formation. One of the benefits of genome mapping is that the genetical determinants of complex characters will be analyzable in an orderly way. Currently, most phenotypic analysis is biometric rather than genetic. For example, the tails of house mice may be shortened by mutations at approximately 40 loci. We know the action of many of these genes: Some affect the notochord, some cell division rates, and some inductive relations between endoderm and mesectoderm. We also know that the tail length of mice varies between different inbred strains of mice (which are similar in the genetic sense to Johannsen’s pure lines) and that we can increase or decrease tail length by selecting wild-caught animals or the products of crosses between inbred strains. We do not know which genes are variable (or segregating) in any one population or which genes are being affected by selection. However, it is clear from many selection experiments that the genes affecting any complex trait are distributed throughout the genome (i.e., over many chromosomes) and that selection for any one trait may ‘‘unbalance’’ the genome. The concept of genomic balance (often called genomic or genetic architecture) is important. When a normal outbreeding species, such as maize, sugar beet, poultry, or Drosophila, is made to inbreed by manipulating its breeding system, the individuals characteristically decline in vigor and fertility until they stabilize at a stage before complete homozygosis is approached. The amount of this inbreeding depression varies from one line to another within any species. When two inbred lines are intercrossed, the F1 (i.e., the first-generation progeny) show a considerable increase in vigor and fertility, known as hybrid vigor or heterosis. In general, the F1 phenotype is similar to that in the population from which the inbred strains were derived. If F2’s are raised and inbreeding is resumed, inbreeding depression will again occur, although not necessarily to the same extent as in the original lines. Inbreeding depression is often reflected in increased variability not only between individuals but also among repetitive parts such as bilateral characters in animals and floral morphology in plants; fluctuating asymmetry, in which there are differences between the right and left sides of individuals, is commonly used as a rough indicator of inbreeding. F1’s tend to show decreased variability. Michael Lerner argued that this indicates an innate superiority of heterozygotes over homozygotes, perhaps because of a greater biochemical flexibility in the former. It is a phenomenon which has produced considerable research interest, particularly among marine biologists. Lerner argued that if artificial selection is suspended before much of the variation has been lost (as homozygosity increases) natural selection will tend to restore the character (and hence its genetic determinants) to an equilibrium value, with the mean of the character which was artificially selected tending to revert toward its original value; he called this genetic homeostasis. Artificial selection tends to accumulate alleles which act on a character in a particular way, e.g., to increase its size of or the number of elements making up a repeated trait. If we make the reasonable assumption that any population needs to combine phenotypic uniformity in a stable environment with
long-term flexibility should the environment change, the easiest way to do this is for the character in question to be controlled by alleles at different loci, with some alleles acting to increase the expression of the character and others acting to decrease it. In such a case, Fisher showed that selection will favor linkage between the loci responsible, with the evolution of ‘‘balanced’’ chromosomes containing ‘‘positive’’ and ‘‘negative’’ alleles. The simplest situation will involve two segregating loci, A,a and B,b with A,B acting in one direction and a,b in the other (i.e., additive genes). The intermediate type can be either the attraction or the repulsion heterozygote, AB/ab or Ab/aB. However, the latter will be favored since it will be less likely to produce zygotes giving the extreme phenotypes (Figure 1). For the same reason, any mechanisms bringing about closer linkage between the loci concerned (such as a chromosomal inversion) will be favored. This theoretical arrangement has been subjected to experimental analysis, mainly through selection experiments in Drosophila, and has been generally confirmed; it receives support from the distribution of ‘‘quantitative trait loci’’ identified by molecular techniques. It also accounts for other properties: 1. Selection (natural or artificial) for any character almost invariably produces correlated responses in additional developmentally independent traits of the phenotype. 2. Gene loci affecting viability traits are interspersed along the chromosomes with loci affecting other characters. 3. The highest rate of artificially induced new variation by mutation is many times less than that occurring spontaneously through recombination. 4. There is widespread occurrence of chromosomal inversions in nature. 5. Deleterious gene combinations (even to the point of lethality) may occur solely as a result of recombination. There are a few cases in which the different genes contributing to complex variation have been identified. This has been done for the determinants of the pin thrum polymorphism in Primula vulgaris, in which different members of a linked group of loci control anther height, style length, pollen size, rate of pollen tube growth, and length of the papillae on the stigma; for mimetic patterns in the African swallowtail butterfly Papilio dardanus; and for color and banding patterns in the land snail Cepaea nemoralis. In house mice, approximately 16% of genes with an identified function are concerned with behavior and have been located on 19 of the 20 chromosomes of the species. However, in most cases it is only possible to conclude that different components of a character complex are inherited as a unit, i.e., that the gene complex is coadapted. Coadaptation is presumably the reason why the genomes of interfertile species do not always merge when they meet. For example, races of dark- and light-bellied house mice (referred to as Mus musculus domesticus and M. m. musculus, respectively, although they should perhaps be given full species status) meet in a narrow zone of intergradation across Jutland (Denmark) and south through Germany. Although the two forms readily interbreed in the laboratory, the hybrid zone has apparently been constant for at least 50 years. Gene frequencies on the two sides of the hybrid zone are very different. Remarkably, the frequencies in the light-bellied form in California, which are descended from the same stock as the light-bellied Danish
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Figure 1 Effect of linkage on the incidence of the extremes of manifestation of an additively inherited character. If A,B produce a phenotype effect of 1 and a,b an effect of 0, the matings between two repulsion heterozygotes are least likely to produce extreme phenotypes (they will only appear if recombination between the two loci occurs in both parents).
animals, are more like those in the light-bellied Danish population than are the light-bellied Danish ones from their dark-bellied neighbors. A similar situation exists in deer mice (Peromyscus polionotus) in Florida and also in carrion and hooded crows in the same area in which the dark- and light-bellied mice occur in Europe. However, some species lose their identity wholly when brought into breeding contact. This has happened commonly in New Zealand, where much of the terrestrial biota has been introduced. Hybrid zones are common. Presumably these occur when coadaptation has not evolved.
Formal Analysis In the past, it was suggested that the genes which control major or qualitative traits are different from those which affect quantitative ones (oligogenes and polygenes, respectively). This distinction is now rarely made. In other words, it is assumed that genes affecting quantitative traits (such as weight or size or physiological properties such as metabolic rate) follow Mendelian patterns of inheritance, may have multiple alleles, can mutate, change in gene frequency, show dominance, etc. Quantitative inheritance is merely a general case of the interaction of genes in which the interacting components are little or wholly known. The number of genes which affect a trait can be estimated by the amount and speed of response in a selection experiment or by the mean and variance of the character as measured in a population. Using these techniques it has been calculated that human skin color may be determined by only 5 or 6 loci,
whereas the number of genes affecting oil and protein production in maize may be as high as 54 and 122, respectively. However, such estimates are very dependent on the nature of interactions between the loci concerned and should be regarded as no more than suggestive of a large or small number. The simplest assumption in multigenic trait determination is that all the loci affect the trait equally and therefore additively. However, detailed analysis has shown that in many (perhaps most) cases, a few genes have a major effect and many genes have a minor effect. For example, in the well-studied case of variation in sternopleural bristle number in D. melanogaster, approximately 10 loci account for 75% of the genetic variation in number. The situation is further complicated by pleiotropy: A gene may have a major effect on one character but minor effects on others. For example, phenylketonuria is an inborn error of metabolism producing severe mental retardation in humans and is produced by the nonfunctioning of phenylalanine hydroxylase, which is controlled as a recessive trait by a single gene on chromosome 12. The same enzyme is involved in melanin synthesis, and phenylketonurics have slightly paler hair and complexion than their normal sibs. The gene can therefore be regarded as having a major effect on intelligence but a minor effect on pigmentation. However, a quantitatively inherited trait will be more likely than a qualitative one to be affected by environment. A group of individuals having identical genes for growth (i.e., a pure line or a clone) may show considerable variation in size due to differences in available nutrients. Although the same potential for size is present in the initial gene products, the manifestation of the phenotype will be limited by such factors as food availability.
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Phenotype, a Historical Perspective
Conversely, a population of genetically heterogeneous individuals may grow to the same size if no gene–environment interaction is limiting (or if different interactions compensate for each other). Generalizing, we can express the phenotypic value P for individual i in environment j as Pij ¼ Gi þ Ej where Gi is the genetic contribution of the jth genotype and Ej is the environmental deviation resulting from the jth environment. A particular genotype may do well in a particular environment, implying a specific interaction between the two. In this case, Pij ¼ Gi þ Ej þ GEij In practice, there will be variance of these components so that Vp ¼ VG þ VE þ 2CovGE where Vp, VG, VE, and 2CovGE, are the phenotypic, genetic, and environmental variance and the genotype–environment covariance, respectively. The genotype–environment covariance is positive when genotypes with higher values are in better environments and poorer genotypes have poorer environments. This may occur in animals when one member of a litter is large because of its genes and gets more food from its parents or when an animal is socially dominant for genetic reasons and therefore has more resources in food and spaces. A plant genotype which grows faster may have a better environment because it is less likely to be shaded. In controlled plant and animal breeding, efforts are made to randomize genotypes and environments, so that CovGE is minimized. In this situation, CovGE can be neglected, and Vp ¼ VG þ VE Conventionally, VG =VP þ VE =VP ¼ h2 þ e2 where h2 and e2 are the proportion of phenotypic variation due to genetic and environmental factors, respectively. The term h2 is known as heritability in the broad sense, h2B ¼ VG =VP In practice the genetic variance is composed of a range of different interactions between loci, which may be additive, dominant, or epistatic. Variability in the narrow sense is defined as h2N ¼ VA =VP where VA is the variance due to additive genetic factors. It is an important statistic in determining the rate and amount of response to directional selection in breeding programs. Heritability is a population-specific measurement. It does not measure an invariant property of a particular trait but only the relative contributions of genetic and environmental differences to phenotypic variation in a specific situation. If either genetic or environmental variation changes, heritability estimates will also change; heritability measures the proportion of phenotypic variation in a particular population due to genetic variation.
Genetic and Phenotypic Variability The assumption of the early geneticists that most populations carry little variation and that most individuals are homozygous at all but a few loci at which alleles are either recent mutants in the process of being eliminated by selection or maintained by opposing selection pressures or heterosis is clearly wrong. Evolutionary theory (requiring modifying genes to change phenotype expression) and artificial selection practice (revealing considerable potential for inherited response to selection) imply the existence of considerable genetic variation in and between populations. In the 1950s and 1960s assumptions about genetic load suggested there was a maximum amount of variation which could be tolerated in any population, but the application of protein and later DNA electrophoresis showed that load theory was too narrow and deterministic and led to reinterpretation so as to incorporate ecological factors (including heterogeneity in time and space and variable stress from biotic and abiotic agents). Empirical data have shown that even inbred organisms (such as obligate self-fertilizers) or ones living in an apparently constant environment (such as the deep sea) may still be heterozygous at a significant proportion of their loci (up to one-fourth for enzyme loci in plants and invertebrates and less for vertebrates). The implications of load theory led to debate among population geneticists and evolutionists about the significance of the observed variation. Theoreticians impressed by the apparent rigor of load theory and biochemists not used to meaningful variation in their study of chemical pathways tended to dismiss the bulk of genetic variation as neutral and irrelevant to the organism, whereas evolutionary ecologists and practical breeders regarded it as potentially adaptive and as expected by Darwinian understanding. The latter emphasis has been shown to be correct: Far from being constrained by invariant genotypes, phenotypes can (and should) be treated as capable of rapid response to the environment and hence permissive rather than determinative of survival. A phenotype can be interpreted as the consequence of developmental reaction norms, facilitated in most cases by the width of its underlying genetic base. This concept is supported by a series of experiments carried out by Bruce Wallace to test if radiation-induced mutations in D. melanogaster were inevitably detrimental. He found that mutations induced in flies made homozygous by artificial breeding were often heterotic, although mutations occurring in flies with a heterozygous background were usually deleterious to their carriers, presumably since their gene expression had been adjusted by normal selection. This led Wallace to emphasize the importance of balancing (or stabilizing) selection rather than the directed or cleansing selection which removes unwanted variants. The concept of reaction norm incorporates the idea of phenotypic plasticity championed by Bradshaw and Levins in the 1960s and provides a much needed synthesis of allometry and ontogeny with ecological realism and fitness components. A particularly good example is the seasonal polyphenism of the African satyrine butterfly, Bicyclus anyana, studied by Paul Brakefield and colleagues. The wet and dry season forms of this species are phenotypically distinct in the size of the
Phenotype, a Historical Perspective
eyespots and the banding patterns on the wings. Seasonal shifts in rainfall are associated with changes in temperature and with butterfly behavior. In the cooler dry season, the insects rest on dry grass or leaf litter and rarely fly; they do not breed at this time. In contrast, the adults fly actively in the warmer wet season, searching for mates and oviposition sites in the lush vegetation. Survival differences between the two forms suggest that cryptic matching is more important in the dry season and deception mediated by the false eyes in the wet season. The wet season form arises through an acceleration of development which can result from an increased or fluctuating temperature, food quality, or hormonal influence. However, eyespot size and plasticity are affected by genetic variation as shown by variation between families in different temperature regimes and by directed selection. The switch between different wing spotting phenotypes in the butterfly Maniola jurtina studied over many years by E. B. Ford is probably also of this nature. Ford’s extensive field studies showed the interaction between founder population differentiation, natural selection in particular localities, and environmental determinants, although he did not interpret them in this way. Unlike the Bicyclus case, the changes in phenotype in Maniola are small and unlikely to be important in survival or fitness (although it would be wrong to be dogmatic about this conclusion). However, they serve as a marker of a variable developmental system which may well have a range of functional responses. There are many such examples of trivial (or even wholly cryptic) differences between individuals which have different functional properties (e.g., the possession of B chromosomes or resistance to a newly introduced pesticide or pathogen). The complicated response system in Bicyclus (and other butterflies) is similar in principle to the much simpler situation of eye pigmentation in the amphipod Gammarus chevreuxi studied classically by Julian Huxley and Ford. Here, the unpigmented, red-eye form is produced by a single mutant allele which has a slower rate of melanin synthesis than normal. However, pigmented eyes like the wild type arise if genetically red-eyed animals are raised at higher temperatures than normal or if they also carry a gene for small eyes which enables the small amount of pigment produced to cover the whole eye. Another example is the ‘‘himalayan’’ mutation of mammals frequently described in elementary genetics textbooks in which an unpigmented (white) coat becomes pigmented at the cold extremities (feet and ears), as in Siamese cats. Pigmentation may also develop in hair which grows in a shaved area which has a lower temperature than usual. The tyrosinase in this genotype is heat labile and has a maximum activity below normal body temperature. Rate genes of this nature have been very important in evolution and can be shown to produce major alterations in body form through various forms of allometry.
Phenotypes and Evolution It is a truism that natural selection can only operate where phenotypic variation exists. Evolution results from changes in gene (strictly allele) frequencies, but these are the consequence rather than the cause of phenotypic differences. It follows that
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selection on local forms (or ecotypes) which are solely the environmental consequence of a particular environment (e.g., plants grown in sheltered or exposed conditions or subject to a particular dietary lack or a behavioral reaction in an animal) will not lead to adaptive adjustment unless the phenotype in question depends on different genotypes. However, a phenotypic response to environmental conditions may allow a genetically nonadapted population to survive long enough to accumulate variants (through mutation, recombination, or immigration) and then adapt genetically. This idea was put forward independently by Baldwin (1896), Osborn (1897), and Lloyd Morgan (1900): It is commonly known as the Principle of Organic Selection or the Baldwin effect. This has been claimed by some to bridge the directed response which is the basis of Lamarckism and the random source of inherited variation which underlies Darwinism. Certainly, it may mimic Lamarckism, although it is of course wholly Darwinian in its operation. Most of the early studies of phenotypic plasticity were carried out by botanists: Gaston Bonnier in the Alps and Pyrenees, F. E. Clements in Colorado and California, Turesson in Sweden, and Clausen, Keck, and Hiesey in California. However, the evolutionary implications were not pursued until Gause and Schmalhaussen in Russia and Waddington in Britain began to examine the relationships between genotype, phenotype, and environment in animal experiments. They were able to show not only that natural selection could lead to a character originally induced by the environment becoming an inherited character (Waddington called this ‘‘genetic assimilation’’) but also that there is a causal connection between the environmentally induced change and subsequent genetic changes. They argued that since adaptabilityFthe ability to acquire an adaptive variant during an animal’s lifetimeFhas a genetic basis, the genes underlying flexible adaptive variations may ultimately be responsible for the evolution of fixed adaptations to a new environment, i.e., the environment is much more than a sieve selecting (or eliminating) chance mutations. These ideas have been criticized (notably by G. C. Williams) on two grounds: That most changes resulting from environmental challenges are not adaptive and that fixation of a genetic response results in a decrease in genetic potential because less (genetic) information is needed to specify a fixed, than a variable response. There is truth in both these objections, although the assumption that plasticity requires more inherited variation than a fixed state is debatable. However, there is no doubt that the link between stress-generated responses and subsequent adaptation requires more study. The problem historically is that ecologists have been primarily concerned with pattern (i.e., spatial relationships within communities), whereas evolutionists have concentrated on processes (i.e., temporal changes within communities), and both have used restrictive definitions of stress. This division between disciplines is not, of course, absolute, but it has led to a rift within population biology and a lack of understanding of coevolutionary possibilities and constraints. The divergence between ecologists and evolutionists is seen in the models developed by each. In general, ecological models are self-contained because the dependent variables (numbers or density) and parameters (birth and death rates, dispersion differences, rates of predation, etc.) are all
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Phenotype, a Historical Perspective
measurable by ecological methods. Ecologists have been particularly concerned with identifying criteria for stability or fluctuation when species interact, for invadability, and for extinction when competition occurs. Such models are limited because the parameters are all manifestations of the phenotypic properties of individuals and hence the product of evolutionary processes. Although lip service is paid to the fact that phenotypes may change, in practice they are assumed to be effectively constant in ecological time. Evolutionary models originally concentrated on examining possible rates of evolution; then they became concerned more with the factors involved in the maintenance of genetic polymorphism. Their variables are the frequencies of alleles and genotypes; their parameters are relative fitnesses and rates of mutation, migration, and recombination. For a long time, fitnesses were regarded by the model builders as virtually constant, and it is only comparatively recently that the dependence of selection coefficients on density and frequency has been incorporated. This false assumption of constancy led to the problems associated with genetic load and to controversies over neutralism. Genetical (evolutionary) models have become increasingly realistic and treat relative fitnesses as capable of varying in time and space as well as with gene frequency and population density. Such models are both genetical and ecological, and therefore they are intrinsically more informative than purely ecological ones. However, they still suffer from a major problem in that they tend to assume a degree of genetical equilibrium or stasis which is unjustified. The way forward will be to increase ecological reality of evolutionary models, taking into account the characteristics of the niche for particular populations and communities, particularly any genetic constraints. Such models obviously need to include behavioral (sociobiological) input and the notion of evolutionary ‘‘strategies.’’
Taxonomy Classification has become increasingly sophisticated with the increase in traits which can be used to characterize a group (or taxon). The problem is that conventional taxonomic (phenotypic) diversity may bear little relationship to genetic diversity. For example, the seaside sparrow (Ammodramus nigrescens) is common on the eastern and southern coasts of the United States. Nine subspecies have been described, including a rare and recently extinct (1987) dusky form, originally regarded as a separate species. Molecular analysis (based on mitochondrial DNA sequences) showed that the dusky sparrow was indistinguishable from other Atlantic forms, but that there was a major and previously unsuspected distinction between Atlantic and Gulf Coast groups.
In contrast, New Zealand tuatara lizards (Sphenodon punctatus) are conventionally treated as a single taxon, but molecular (and morphological) criteria indicate they comprise at least three species. For conservation management, it is obviously important that each taxon be considered separately. There is no clear correlation between genetic and taxonomic diversity. The problems of classification that have always challenged museum workers have been compounded by the possibility of using genetic factors as additional or substitute taxonomic criteria: Closely related species in the genetic sense may have very different niches than those of their near relatives, whereas genetically more distant forms may look alike and interact strongly. There are no clear rules to link phenotype with genotype or phenotypic variety with genetic variety. There is plenty of scope for better multidisciplinary understanding of phenotypes, this will have to involve genetics, development, behavior, biotic and abiotic environments, life history, and phylogeny. Notwithstanding case by case examinations of the determinants and plasticity of the phenotypes in particular species and species groups are still needed.
See also: Evolution, Theory of. Genes, Description of. Genetic Diversity
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